tbuckley/cabot-search huggingface dataset:
Digital health and acute kidney injury: consensus report of the 27th Acute Disease Quality Initiative workgroup
Authors: Kianoush B. Kashani, Linda Awdishu, Sean M. Bagshaw, Erin F. Barreto, Rolando Claure-Del Granado, Barbara J. Evans, Lui G. Forni, Erina Ghosh, Stuart L. Goldstein, Sandra L. Kane-Gill, Jejo Koola, Jay L. Koyner, Mei Liu, Raghavan Murugan, Girish N. Nadkarni, Javier A. Neyra, Jacob Ninan, Marlies Ostermann, Neesh Pannu, Parisa Rashidi, Claudio Ronco, Mitchell H. Rosner, Nicholas M. Selby, Benjamin Shickel, Karandeep Singh, Danielle E. Soranno, Scott M. Sutherland, Azra Bihorac, Ravindra L. Mehta
Journal: Nature Reviews Nephrology (2023)

Acute kidney injury (AKI), which is a common complication of acute illnesses, affects the health of individuals in community, acute care and post-acute care settings. Although the recognition, prevention and management of AKI has advanced over the past decades, its incidence and related morbidity, mortality and health care burden remain overwhelming. The rapid growth of digital technologies has provided a new platform to improve patient care, and reports show demonstrable benefits in care processes and, in some instances, in patient outcomes. However, despite great progress, the potential benefits of using digital technology to manage AKI has not yet been fully explored or implemented in clinical practice. Digital health studies in AKI have shown variable evidence of benefits, and the digital divide means that access to digital technologies is not equitable. Upstream research and development costs, limited stakeholder participation and acceptance, and poor scalability of digital health solutions have hindered their widespread implementation and use. Here, we provide recommendations from the Acute Disease Quality Initiative consensus meeting, which involved experts in adult and paediatric nephrology, critical care, pharmacy and data science, at which the use of digital health for risk prediction, prevention, identification and management of AKI and its consequences was discussed. In this Consensus Statement, the authors discuss a framework for the development, validation and implementation of digital health technologies across the acute kidney injury continuum — risk prediction, prevention, detection and management.
Single-cell analysis reveals key differences between early-stage and late-stage systemic sclerosis skin across autoantibody subgroups
Authors: Kristina Elizabeth Neergaard Clark, Shiwen Xu, Moustafa Attah, Voon H Ong, Christopher Dominic Buckley, Christopher P Denton
Journal: Annals of the Rheumatic Diseases (2023)

The severity of skin involvement in diffuse cutaneous systemic sclerosis (dcSSc) depends on stage of disease and differs between anti-RNA-polymerase III (ARA) and anti-topoisomerase antibody (ATA) subsets. We have investigated cellular differences in well-characterised dcSSc patients compared with healthy controls (HCs).We performed single-cell RNA sequencing on 4 mm skin biopsy samples from 12 patients with dcSSc and HCs (n=3) using droplet-based sequencing (10× genomics). Patients were well characterised by stage (>5 or <5 years disease duration) and autoantibody (ATA+ or ARA+). Analysis of whole skin cell subsets and fibroblast subpopulations across stage and ANA subgroup were used to interpret potential cellular differences anchored by these subgroups.Fifteen forearm skin biopsies were analysed. There was a clear separation of SSc samples, by disease, stage and antibody, for all cells and fibroblast subclusters. Further analysis revealed differing cell cluster gene expression profiles between ATA+ and ARA+ patients. Cell-to-cell interaction suggest differing interactions between early and late stages of disease and autoantibody. TGFβ response was mainly seen in fibroblasts and smooth muscle cells in early ATA+dcSSc skin samples, whereas in early ARA+dcSSc patient skin samples, the responding cells were endothelial, reflect broader differences between clinical phenotypes and distinct skin score trajectories across autoantibody subgroups of dcSSc.We have identified cellular differences between the two main autoantibody subsets in dcSSc (ARA+ and ATA+). These differences reinforce the importance of considering autoantibody and stage of disease in management and trial design in SSc.
Annals of the Rheumatic Diseases collection on autoantibodies in the rheumatic diseases: new insights into pathogenesis and the development of novel biomarkers
Authors: David S Pisetsky
Journal: Annals of the Rheumatic Diseases (2023)

The rheumatic diseases are a diverse group of conditions that can display autoantibody production, functional immune disturbances and systemic disease manifestations. These autoantibodies can serve as markers for classification, diagnosis, prognosis and disease activity. Among specificities prominently expressed by patients, those directed to nuclear antigens (antinuclear antibodies or ANAs) are markers for specific rheumatic diseases. ANAs can bind to DNA, RNA and complexes of proteins with nucleic acids. Other autoantibodies expressed in the rheumatic diseases are directed to proteins, including IgG, post-translational modifications of proteins and soluble mediators such as cytokines. While autoantibodies have been investigated for over 50 years, recent studies published in the
Inequities in kidney health and kidney care
Authors: Raymond Vanholder, Lieven Annemans, Marion Braks, Edwina A. Brown, Priya Pais, Tanjala S. Purnell, Simon Sawhney, Nicole Scholes-Robertson, Bénédicte Stengel, Elliot K. Tannor, Vladimir Tesar, Arjan van der Tol, Valérie A. Luyckx
Journal: Nature Reviews Nephrology (2023)
The Effect of Low-Dose Glucocorticoids Over Two Years on Weight and Blood Pressure in Rheumatoid Arthritis: Individual Patient Data From Five Randomized Trials
Authors: Andriko Palmowski, Sabrina M. Nielsen, Zhivana Boyadzhieva, Linda Hartman, Judith Oldenkott, Björn Svensson, Ingiäld Hafström, Siegfried Wassenberg, Ernest Choy, John Kirwan, Robin Christensen, Maarten Boers, Frank Buttgereit
Journal: Annals of Internal Medicine (2023)

Weight gain and hypertension are well known adverse effects of treatment with high-dose glucocorticoids.To evaluate the effects of 2 years of low-dose glucocorticoid treatment in rheumatoid arthritis (RA).Pooled analysis of 5 randomized controlled trials with 2-year interventions allowing concomitant treatment with disease-modifying antirheumatic drugs.12 countries in Europe.Early and established RA.Glucocorticoids at 7.5 mg or less prednisone equivalent per day.Coprimary end points were differences in change from baseline in body weight and mean arterial pressure after 2 years in intention-to-treat analyses. Difference in the change of number of antihypertensive drugs after 2 years was a secondary end point. Subgroup and sensitivity analyses were done to assess the robustness of primary findings.A total of 1112 participants were included (mean age, 61.4 years [SD, 14.5]; 68% women). Both groups gained weight in 2 years, but glucocorticoids led, on average, to 1.1 kg (95% CI, 0.4 to 1.8 kg; P < 0.001) more weight gain than the control treatment. Mean arterial pressure increased by about 2 mm Hg in both groups, with a between-group difference of -0.4 mm Hg (CI, -3.0 to 2.2 mm Hg; P = 0.187). These results were consistent in sensitivity and subgroup analyses. Most patients did not change the number of antihypertensive drugs, and there was no evidence of differences between groups.Body composition was not assessed, and generalizability to non-European regions may be limited.This study provides robust evidence that low-dose glucocorticoids, received over 2 years for the treatment of RA, increase weight by about 1 kg but do not increase blood pressure.None.
Oleoylethanolamide facilitates PPARα and TFEB signaling and attenuates Aβ pathology in a mouse model of Alzheimer’s disease
Authors: Michele M. Comerota, Manasee Gedam, Wen Xiong, Feng Jin, Lisheng Deng, Meng C. Wang, Jin Wang, Hui Zheng
Journal: Molecular Neurodegeneration (2023)

Abstract Background Age is the strongest risk factor for the development of Alzheimer’s disease (AD). Besides the pathological hallmarks of β-amyloid (Aβ) plaques and neurofibrillary tangles, emerging evidence demonstrates a critical role of microglia and neuroinflammation in AD pathogenesis. Oleoylethanolamide (OEA) is an endogenous lipid amide that has been shown to promote lifespan and healthspan in C. elegans through regulation of lysosome-to-nucleus signaling and cellular metabolism. The goal of our study was to determine the role of OEA in the mediation of microglial activity and AD pathology using its stable analog, KDS-5104. Methods We used primary microglial cultures and genetic and pharmacological approaches to examine the signaling mechanisms and functional roles of OEA in mediating Aβ phagocytosis and clearance, lipid metabolism and inflammasome formation. Further, we tested the effect of OEA in vivo in acute LPS-induced neuroinflammation and by chronic treatment of 5xFAD mice. Results We found that OEA activates PPARα signaling and its downstream cell-surface receptor CD36 activity. In addition, OEA promotes TFEB lysosomal function in a PPARα-dependent but mTORC1-independent manner, the combination of which leads to enhanced microglial Aβ uptake and clearance. These are associated with the suppression of LPS-induced lipid droplet accumulation and inflammasome activation. Chronic treatment of 5xFAD mice with KDS-5104 restored dysregulated lipid profiles, reduced reactive gliosis and Aβ pathology and rescued cognitive impairments. Conclusion Together, our study provides support that augmenting OEA-mediated lipid signaling may offer therapeutic benefit against aging and AD through modulating lipid metabolism and microglia phagocytosis and clearance.
Poly-l-glutamic acid modification modulates the bio-nano interface of a therapeutic anti-IGF-1R antibody in prostate cancer
Authors: Sonia Vicente-Ruiz, Ana Armiñán, Katia Maso, Elena Gallon, Oleksandr Zagorodko, Julie Movellan, Fernanda Rodríguez-Otormín, Maike Baues, Jan-Niklas May, Federica De Lorenzi, Twan Lammers, María J. Vicent
Journal: Biomaterials (2023)

Modifying biological agents with polymers such as polyethylene glycol (PEG) has demonstrated clinical benefits; however, post-market surveillance of PEGylated derivatives has revealed PEG-associated toxicity issues, prompting the search for alternatives. We explore how conjugating a poly-l-glutamic acid (PGA) to an anti-insulin growth factor 1 receptor antibody (AVE1642) modulates the bio-nano interface and anti-tumor activity in preclinical prostate cancer models. Native and PGA-modified AVE1642 display similar anti-tumor activity in vitro; however, AVE1642 prompts IGF-1R internalization while PGA conjugation prompts higher affinity IGF-1R binding, thereby inhibiting IGF-1R internalization and altering cell trafficking. AVE1642 attenuates phosphoinositide 3-kinase signaling, while PGA-AVE1642 inhibits phosphoinositide 3-kinase and mitogen-activated protein kinase signaling. PGA conjugation also enhances AVE1642's anti-tumor activity in an orthotopic prostate cancer mouse model, while PGA-AVE1642 induces more significant suppression of cancer cell proliferation/angiogenesis than AVE1642. These findings demonstrate that PGA conjugation modulates an antibody's bio-nano interface, mechanism of action, and therapeutic activity.
Right Atrial Adaptation to Precapillary Pulmonary Hypertension
Authors: Jeroen N. Wessels, Jessie van Wezenbeek, Jari de Rover, Rowan Smal, Aida Llucià-Valldeperas, Lucas R. Celant, J. Tim Marcus, Lilian J. Meijboom, Joanne A. Groeneveldt, Frank P.T. Oosterveer, Toon A. Winkelman, Hans W.M. Niessen, Marie-José Goumans, Harm Jan Bogaard, Anton Vonk Noordegraaf, Gustav J. Strijkers, M. Louis Handoko, Berend E. Westerhof, Frances S. de Man
Journal: Journal of the American College of Cardiology (2023)

Precapillary pulmonary hypertension (precPH) patients have altered right atrial (RA) function and right ventricular (RV) diastolic stiffness. This study aimed to investigate RA function using pressure-volume (PV) loops, isolated cardiomyocyte, and histological analyses. RA PV loops were constructed in control subjects (n = 9) and precPH patients (n = 27) using magnetic resonance and catheterization data. RA stiffness (pressure rise during atrial filling) and right atrioventricular coupling index (RA minimal volume / RV end-diastolic volume) were compared in a larger cohort of patients with moderate (n = 39) or severe (n = 41) RV diastolic stiffness. Cardiomyocytes were isolated from RA tissue collected from control subjects (n = 6) and precPH patients (n = 9) undergoing surgery. Autopsy material was collected from control subjects (n = 6) and precPH patients (n = 4) to study RA hypertrophy, capillarization, and fibrosis. RA PV loops showed 3 RA cardiac phases (reservoir, passive emptying, and contraction) with dilatation and elevated pressure in precPH. PrecPH patients with severe RV diastolic stiffness had increased RA stiffness and worse right atrioventricular coupling index. Cardiomyocyte cross-sectional area was increased 2- to 3-fold in precPH, but active tension generated by the sarcomeres was unaltered. There was no increase in passive tension of the cardiomyocytes, but end-stage precPH showed reduced number of capillaries per mm2 accompanied by interstitial and perivascular fibrosis. RA PV loops show increased RA stiffness and suggest atrioventricular uncoupling in patients with severe RV diastolic stiffness. Isolated RA cardiomyocytes of precPH patients are hypertrophied, without intrinsic sarcomeric changes. In end-stage precPH, reduced capillary density is accompanied by interstitial and perivascular fibrosis.
Return-to-Play for Elite Athletes With Genetic Heart Diseases Predisposing to Sudden Cardiac Death
Authors: Katherine A. Martinez, J. Martijn Bos, Aaron L. Baggish, Dermot M. Phelan, Kathryn E. Tobert, Darrel B. Newman, Erica Scherer, Bradley J. Petek, Michael J. Ackerman, Matthew W. Martinez
Journal: Journal of the American College of Cardiology (2023)
ACC/AHA and ESC/EACTS Guidelines for the Management of Valvular Heart Diseases
Authors: Augustin Coisne, Patrizio Lancellotti, Gilbert Habib, Madalina Garbi, Jordi Sanchez Dahl, Marco Barbanti, Mani A. Vannan, Vassilios S. Vassiliou, Dariusz Dudek, Ovidiu Chioncel, Johannes L. Waltenberger, Victoria L. Johnson, Ruggero De Paulis, Rodolfo Citro, Philippe Pibarot
Journal: Journal of the American College of Cardiology (2023)
Risk of Arrhythmic Death in Patients With Nonischemic Cardiomyopathy
Authors: Jonathan Chrispin, Faisal M. Merchant, Neal K. Lakdawala, Katherine C. Wu, Gordon F. Tomaselli, Rachita Navara, Estelle Torbey, Amrut V. Ambardekar, Rajesh Kabra, Eloisa Arbustini, Jagat Narula, Maya Guglin, Christine M. Albert, Sumeet S. Chugh, Natalia Trayanova, Jim W. Cheung
Journal: Journal of the American College of Cardiology (2023)
Bleeding and Ischemic Risks of Ticagrelor Monotherapy After Coronary Interventions
Authors: Guiomar Mendieta, Shamir Mehta, Usman Baber, Dominick J. Angiolillo, Carlo Briguori, David Cohen, Timothy Collier, George Dangas, Dariusz Dudek, Javier Escaned, Robert Gil, Birgit Vogel, Davide Cao, Alessandro Spirito, Kurt Huber, Adnan Kastrati, Upendra Kaul, Ran Kornowski, Mitchell W. Krucoff, Vijay Kunadian, David J. Moliterno, E. Magnus Ohman, Gennaro Sardella, Samantha Sartori, Samin Sharma, Richard Shlofmitz, P. Gabriel Steg, Ya-Ling Han, Stuart Pocock, C. Michael Gibson, Roxana Mehran
Journal: Journal of the American College of Cardiology (2023)
The Complete Blood Count: Increasing Its Precision and Impact
Authors: Stephen D. Sisson
Journal: Annals of Internal Medicine (2023)

LettersAugust 2023The Complete Blood Count: Increasing Its Precision and ImpactStephen D. Sisson, MDStephen D. Sisson, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L23-0163 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR: Although I applaud Burack and Lichtman's (1) goal of streamlining the CBC, they have perhaps gone too far. For example, leaving out the RBC count will challenge distinguishing microcytic anemia due to iron deficiency (associated with a low RBC count) from any of the thalassemias (typically associated with a high or high-normal RBC count). Hereditary spherocytosis will also be missed without the MCHC. I understand that a quick CBC in an acutely ill patient may not need these measurements, but they add value and should not be removed from the CBC.Reference1. Burack WR, Lichtman MA. The complete blood count: increasing its precision and impact [Editorial]. Ann Intern Med. 2023;176:404-405. [PMID: 36716452] doi:10.7326/M22-3071 LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: Stephen D. Sisson, MDDisclosures: Authors have reported no disclosures of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L23-0163. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoThe Complete Blood Count: Increasing Its Precision and Impact W. Richard Burack and Marshall A. Lichtman The Complete Blood Count: Increasing Its Precision and Impact Marko Lucijanic , and Ivan Krecak The Complete Blood Count: Increasing Its Precision and Impact W. Richard Burack , and Marshall A. Lichtman Metrics August 2023Volume 176, Issue 8KeywordsAnemiaComplete blood countHematocritIron deficiencyMean corpuscular hemoglobinMean corpuscular hemoglobin concentrationMean corpuscular volumeRed blood cellsReticulocytesWhite blood cells ePublished: 15 August 2023 Issue Published: August 2023 Copyright & PermissionsCopyright © 2023 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Efficacy and safety of a targeted-release formulation of budesonide in patients with primary IgA nephropathy (NefIgArd): 2-year results from a randomised phase 3 trial
Authors: Richard Lafayette, Jens Kristensen, Andrew Stone, Jürgen Floege, Vladimir Tesař, Hernán Trimarchi, Hong Zhang, Necmi Eren, Alexander Paliege, Heather N Reich, Brad H Rovin, Jonathan Barratt
Journal: The Lancet (2023)
Treatment of pulmonary arterial hypertension: recent progress and a look to the future
Authors: Marc Humbert, Olivier Sitbon, Christophe Guignabert, Laurent Savale, Athénaïs Boucly, Mélanie Gallant-Dewavrin, Vallerie McLaughlin, Marius M Hoeper, Jason Weatherald
Journal: The Lancet Respiratory Medicine (2023)
First-line cemiplimab monotherapy and continued cemiplimab beyond progression plus chemotherapy for advanced non-small-cell lung cancer with PD-L1 50% or more (EMPOWER-Lung 1): 35-month follow-up from a mutlicentre, open-label, randomised, phase 3 trial
Authors: Mustafa Özgüroğlu, Saadettin Kilickap, Ahmet Sezer, Mahmut Gümüş, Igor Bondarenko, Miranda Gogishvili, Marina Nechaeva, Michael Schenker, Irfan Cicin, Gwo Fuang Ho, Yaroslav Kulyaba, Kasimova Zyuhal, Roxana-Ioana Scheusan, Marina Chiara Garassino, Xuanyao He, Manika Kaul, Emmanuel Okoye, Yuntong Li, Siyu Li, Jean-Francois Pouliot, Frank Seebach, Israel Lowy, Giuseppe Gullo, Petra Rietschel
Journal: The Lancet Oncology (2023)
Annals Consult Guys - Management of Dual-Antiplatelet Therapy in a Patient Undergoing Colonoscopy
Authors: Howard H. Weitz, Geno J. Merli, David L. Fischman
Journal: Annals of Internal Medicine (2023)

Web ExclusivesAugust 2023Annals Consult Guys - Management of Dual-Antiplatelet Therapy in a Patient Undergoing ColonoscopyFREEHoward H. Weitz, MD, Geno J. Merli, MD, and David L. Fischman, MDHoward H. Weitz, MDThomas Jefferson University, Philadelphia, Pennsylvania (H.H.W., G.J.M.)Search for more papers by this author, Geno J. Merli, MDThomas Jefferson University, Philadelphia, Pennsylvania (H.H.W., G.J.M.)Search for more papers by this author, and David L. Fischman, MDThomas Jefferson University Hospital, Philadelphia, Pennsylvania (D.L.F.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W22-0021 CME/MOC SectionsSupplemental MaterialAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The Annals Consult Guys discuss the pericolonoscopy management of a patient on dual-antiplatelet therapy and oral anticoagulation following percutaneous transluminal coronary angioplasty (PTCA) with placement of a drug-eluting stent.For more videos from and information on Annals Consult Guys, visit go.annals.org/ConsultGuys. Comments0 CommentsSign In to Submit A Comment VINCENT S. PANELLA, MDnone15 August 2023 What is the answer? Perhaps I missed it but what was the final recommendation for the patient in the presentation as to his DOAC and antiplatelet therapy before the colonoscopy? Since it was 5 months after his stent for stable CAD can we wait one more month to perform his colonoscopy on ASA alone and hold his DOAC for 3 days prior? Author, Article, and Disclosure InformationAuthors: Howard H. Weitz, MD; Geno J. Merli, MD; David L. Fischman, MDAffiliations: Thomas Jefferson University, Philadelphia, Pennsylvania (H.H.W., G.J.M.)Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (D.L.F.)Disclosures: Drs. Merli and Weitz report that they have no financial relationships or interests to disclose. Dr. Fischman reports Pfizer stock or stock options that have no relationship to the topic of discussion in this episode. All relevant financial relationships have been mitigated. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=W22-0021.Editors' Disclosures: The editors have no relevant financial relationships to disclose. Individual forms may be viewed at www.annals.org/editorsdisclosures. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics August 2023Volume 176, Issue 8 ePublished: 15 August 2023 Issue Published: August 2023 Copyright & PermissionsCopyright © 2023 by American College of Physicians. All Rights Reserved.Loading ...